During the past 4 years since the last comprehensive progress report we have proven that GI hormones directly influence growth of GI mucosa and that gastrin is an important physiological stimulator of growth of oxyntic gland, small intestinal and colonic mucosa. In addition we have worked out much of the biochemical response involved in the mechanism of gastrin's stimulation of the pleiotypic response. We have also established that the pituitary and growth hormone play a significant role in regulating endogenous gastrin levels. This work will be extended in the current proposal by pursuing the following areas: (1) Examination of additional GI peptides and hormones, (2) Determination of the role of parasympathetic innervation regulating growth of GI mucosae, (3) Determination of inter-relationships of ACTH, cortisol, growth hormone and gastrin in regulating growth of GI mucosae, (4) Development of a receptor assay for gastrin binding to mucosal membranes and relationship of binding to trophic activity and cyclic nucleotides, (5) Mucosal tissue from patients with gastric ulcer, pernicious anemia, atrophic gastritis or cancer will be cultured and its growth and gastrin binding characteristics studied, (6) The identity of proteins whose synthesis is stimulated by gastrin will be studied using polyacrylamide SDS gel electrophoresis. The overall objective of this project is to define and understand the factors regulating the growth of gastrointestinal mucosa with a special emphasis on gastrointestinal hormones.